Following the creation of a new De Novo classification request user fee under the fourth iteration of the Medical Device User Fee Amendments (MDUFA IV) of $93,017 (small businesses pay $23,254), the US Food and Drug Administration (FDA) on Friday released one final guidance and one draft guidance.
The draft and final guidance come as FDA has seen an increased De Novo submission volume, from 42 submissions in 2014 to 69 in 2017.
The draft guidance, when finalized, will provide FDA staff with clearer approach to making "Accept" or "Refuse to Accept" (RTA) decisions on De Novo requests for medical devices, while the final guidance discusses the process for submitting and reviewing a classification request.
The De Novo pathway allows for a Class I or Class II classification for medical devices for which general controls or general and special controls provide a reasonable assurance of safety and effectiveness, but for which there is no legally marketed predicate device.
The Food and Drug Administration Modernization Act of 1997 (FDAMA) added the De Novo classification as an alternate option to classifying novel devices automatically placed in Class III after receiving a "not substantially equivalent" (NSE) determination in response to a 510(k) submission. The Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012 later allowed sponsors to submit a De Novo classification request to the FDA without first being required to submit a 510(k).
According to FDA, there are two options for De Novo classification for novel devices of low to moderate risk:
- "Any person who receives an NSE determination in response to a 510(k) submission may, within 30 days of receipt of the NSE determination, submit a De Novo request for the FDA to make a risk-based evaluation for classification of the device into Class I or II."
- "Any person who determines that there is no legally marketed device upon which to base a determination of substantial equivalence may submit a De Novo request for the FDA to make a risk-based classification of the device into Class I or II, without first submitting a 510(k) and receiving an NSE determination."
But the 21st Century Cures Act removed the requirement that a De Novo request be submitted within 30 days of receiving an NSE determination, and the final guidance issued on Friday reflects that change.
With the enactment of MDUFA IV, FDA also agreed to new performance goals based on the timeliness of reviews and a submission checklist to make the reviews more efficient and timely.
The 30-page draft guidance explains the procedures and criteria that the FDA intends to use in assessing whether a De Novo classification request is sufficiently complete for a substantive review. The initial acceptance review will take no more than 15 days, FDA says.
While acknowledging that it anticipates that the agency and industry may need up to 60 days to perform activities to operationalize the policies within the guidance, when finalized, the draft includes both an acceptance checklist appendix for De Novo classification requests and a recommended content checklist appendix.
The acceptance checklist is to ensure the request contains the necessary information to conduct a substantive review, and the draft says FDA "should not refuse to accept a De Novo request if information is present but inadequate to support granting the De Novo request."
The De Novo requester also may provide a rationale for why any criteria in the checklist are not applicable to the device, FDA says, though the agency expects that each item in the Acceptance Checklist will be addressed either by "including the requested information or providing a rationale for why is it not applicable or why there is a deviation."
FDA also discusses the review clock for De Novo requests, noting if the De Novo request is accepted for substantive review on the first acceptance review, the FDA review clock start date is the FDA document center’s receipt date of the request. However, if the De Novo request is designated RTA, the FDA review clock start date will be the document center’s receipt date of the De Novo request including the additional information that results in an acceptance designation, "even if FDA later requests information that should have been requested during acceptance review."
Once the De Novo request is under substantive review, the up to 15 calendar days used to conduct the acceptance review are included within the total calendar days to reach a final decision for the De Novo request.
The final version of another De Novo guidance, which supersedes guidance from 1998, and describes the De Novo classification process, also provides more details clarifying descriptions of the classification process and explains that in the situation when a company first submits a 510(k), the 21st Century Cures Act removed the requirement that a De Novo request be submitted within 30 days of receiving a not substantially equivalent (NSE) determination.
Here’s a chart featured in the first attachment of the guidance, describing the classification process:
Acceptance Review for De Novo Classification Requests Draft Guidance for Industry and Food and Drug Administration Staff
De Novo Classification Process (Evaluation of Automatic Class III Designation) Guidance for Industry and Food and Drug Administration Staff
De Novo summary documents